This International Myeloma Working Group consensus updates the disease defi nition of multiple myeloma to include validated biomarkers in addition to existing requirements of attributable CRAB features (hypercalcaemia, renal failure, anaemia, and bone lesions). These changes are based on the identifi cation of biomarkers associated with near inevitable development of CRAB features in patients who would otherwise be regarded as having smouldering multiple myeloma. A delay in application of the label of multiple myeloma and postponement of therapy could be detrimental to these patients. In addition to this change, we clarify and update the underlying laboratory and radiographic variables that fulfi l the criteria for the presence of myeloma-defi ning CRAB features, and the histological and monoclonal protein requirements for the disease diagnosis. Finally, we provide specifi c metrics that new biomarkers should meet for inclusion in the disease defi nition. The International Myeloma Working Group recommends the implementation of these criteria in routine practice and in future clinical trials, and recommends that future studies analyse any diff erences in outcome that might occur as a result of the new disease defi nition.

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Treatments for myeloma have expanded in the last decade, but it is not clear if the introduction of novel therapies and the increased use of high-dose therapy have translated into better outcome for patients with myeloma. We examined the outcome of 2 groups of patients seen at a single institution, one from time of diagnosis and the other from the time of relapse, to examine the survival trends over time. Among 387 patients relapsing after stemcell transplantation, a clear improvement in overall survival from the time of relapse was seen, with those relapsing after 2000 having a median overall survival of 23.9 versus 11.8 months (P < .001) for those who relapsed prior to this date. This improvement was independent of other prognostic factors. Patients treated with one or more of the newer drugs (thalidomide, lenalidomide, bortezomib) had longer survival from relapse (30.9 vs 14.8 months; P < .001). In a larger group of 2981 patients with newly diagnosed myeloma, those diagnosed in the last decade had a 50% improvement in overall survival (44.8 vs 29.9 months; P < .001). In this study, we demonstrate improved outcome of patients with myeloma in recent years, both in the relapsed setting as well as at diagnosis. IntroductionMultiple myeloma (MM), a neoplasm of plasma cells, affects 1 to 5 per 100 000 individuals each year worldwide with a higher incidence in the West. 1 It is the second most common hematologic malignancy in the United States, and it is estimated that there will be 19 900 new diagnoses and 10 790 deaths due to myeloma in 2007. 2 The median survival of patients with MM was less than a year before introduction of alkylating agents, and the introduction of melphalan in the 1960s resulted in improved survival. 3,4 A timeline of major therapeutic advances in multiple myeloma is outlined in Table 1. In the 1980s, introduction of high-dose chemotherapy and stem-cell rescue (ASCT) was introduced, and randomized trials since have demonstrated a survival advantage for this modality compared with conventional chemotherapy (CCT). [5][6][7] The introduction of thalidomide represented a major milestone in the treatment of myeloma, and the subsequent availability of its analog lenalidomide and the proteasome inhibitor bortezomib have expanded the therapeutic armamentarium for myeloma. [8][9][10][11][12] Incorporation of these novel agents has resulted in a paradigm shift in the treatment of myeloma, with their use earlier in the disease course. 13 While the new drugs have allowed successful salvage of relapsed disease, it is not clear if the survival of patients has improved during the last few years. We examined patients seen at our institution over a 36-year period to determine whether there has been an improvement in survival of myeloma patients seen during this time period. MethodsWe examined 2 cohorts of patients seen at Mayo Clinic with a diagnosis of MM. The first cohort consisted of 387 patients who were examined for potential improvement in survival following first relapse after ASCT. These patients we...

Purpose The clinical outcome of multiple myeloma (MM) is heterogeneous. A simple and reliable tool is needed to stratify MM patients. We combined the International Staging System (ISS) with chromosomal abnormalities (CA) detected by interphase Fluorescence In Situ Hybridization (iFISH) after CD138 plasma cells purification and serum lactate dehydrogenase (LDH) to evaluate their prognostic value in newly diagnosed MM (NDMM). Methods Clinical and laboratory data from 4445 NDMM patients enrolled in eleven international trials were pooled together. The K-adaptive partitioning algorithm was used to define the most appropriate subgroups with homogeneous survival. Results ISS, CA, and LDH data were simultaneously available in 3060/4445 patients. We defined three groups: revised ISS (R-ISS) I (N=871), including ISS I (serum β2-microglobulin level <3.5mg/L and serum albumin level ≥3.5g/dL), no high-risk CA [del(17p) and/or t(4;14) and/or t(14;16)] and normal LDH level (below the upper limit of normal range); R-ISS III (N=295), including ISS III (serum β2-microglobulin level >5.5mg/L) and high-risk CA or high LDH level; R-ISS II (N=1894), including all the other possible combinations. At a median follow-up of 46 months, the 5-year OS was 82% in the R-ISS I, 62% in the R-ISS II, and 40% in the R-ISS III groups; the 5-year PFS was 55%, 36% and 24%, respectively. Conclusions The R-ISS is a simple and powerful prognostic staging system and we recommend its use in future clinical studies to stratify NDMM patients effectively with respect to the relative risk to their survival.

We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms.